Liquid delivery device, liquid chromatograph, and method for operation of liquid delivery device

ABSTRACT

The present invention provides a liquid delivery device for liquid chromatographs which, by performing liquid delivery at an accurate flow rate with limited pulsation, gives accurate results of analyses. The present invention, with a view to preventing erroneous operation due to errors in measurements at the time of judgment of completion of compression of liquid, establishes the judgment point before the pressure measured by a cylinder pressure detector agrees with the pressure measured by a discharge pressure detector and also calculates the point of completion of compression. Control in this manner prevents pressure fluctuation. It also calculates for control the point of completion of compression from the history of compression performed previously.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a liquid delivery device, a liquidchromatograph, and a method for operation of said liquid deliverydevice.

2. Description of the Related Art

Any liquid chromatograph is provided with a liquid delivery device,among which is that of reciprocating plunger type. A conventional one ofthat type usually has two cylinders in each of which a plungerreciprocates, so that it delivers a liquid continuously, with twocylinders repeating sucking and discharging alternately.

Liquid delivery in this manner takes a certain length of time until thecylinder pressure reaches the discharge pressure because the liquid iscompressed when the liquid, which has been suck up into the cylinder, isforced out by the plunger. As soon as the liquid is pressurized and thecylinder pressure reaches the discharge pressure, the valve at thedischarge side is opened to deliver the liquid.

The drawback of such operation lies in the difficulties of detectingthat the cylinder pressure is equal to the discharge pressure and theerror of detection that prevents accurate control. This drawback leadsto pulsation of liquid delivery that occurs in synchronism with thefrequency of plunger movements. Such pulsation causes errors in liquidchromatography as described in Patent Documents 1 and 2.

Patent Document 1: Japanese Patent No. 3491948

Patent Document 2: Japanese Patent No. 3709409

OBJECT AND SUMMARY OF THE INVENTION

The present invention was completed in view of the foregoing. It is anobject of the present invention to provide a liquid delivery device, aliquid chromatograph, and a method for operation of said liquid deliverydevice.

The present invention is directed to an improved liquid delivery devicehaving a plurality of cylinders, each with a reciprocating plunger, amotor to drive said plunger, a control unit to control operation of saidmotor, a discharge pressure detector to measure the discharge pressureof the eluent being discharged from said cylinders, and a cylinderpressure detector to measure the pressure of said eluent flowing in saidcylinders, wherein said improvement is characterized in that saidcontrol unit establishes the judgment point before the pressure measuredby said cylinder pressure detector agrees with the pressure measured bysaid discharge pressure detector and controls the speed of rotation ofsaid motor on the basis of the discharge pressure measured by saiddischarge pressure detector and the pressure measured by said cylinderpressure detector.

The present invention is directed also to an improved liquid deliverydevice having cylinders arranged in series in more than one stage,plungers reciprocating in said cylinders arranged in more than onestage, a motor to drive said plungers, a control unit to controloperation of said motor, a discharge pressure detector to control thedischarge pressure of the eluent discharged from the cylinder in thelast stage, and a cylinder pressure detector to measure the pressure ofsaid eluent flowing in the cylinder in the initial or middle stage,wherein said improvement is characterized in that said control unitcontrols the speed of rotation of said motor on the basis of thedischarge pressure measured by said discharge pressure detector and thepressure measured by said cylinder pressure detector.

The present invention is directed also to an improved liquid deliverydevice having a plurality of cylinders, each with a reciprocatingplunger, a motor to drive said plunger, a control unit to controloperation of said motor, a supply flow channel to supply the eluent fromthe supply source to said cylinder that functions as a supplier, aninlet check valve attached to said supply channel, an intermediate flowchannel to lead said eluent, which has been pressurized in multiplestages including cylinders at said supply side, to said cylinder in thefinal stage, an outlet check valve attached to said intermediate flowchannel, a discharge pressure detector to measure the discharge pressureof said eluent being discharged from said cylinder in the final stage,and a cylinder pressure detector to measure the pressure of said eluentflowing in said cylinders excluding said cylinder in the final stage,wherein said improvement is characterized in that said control unitestablishes the judgment point before the pressure measured by the saidcylinder pressure detector agrees with the pressure measured by saiddischarge pressure detector and controls the speed of rotation of saidmotor on the basis of the discharge pressure measured by said dischargepressure detector and the pressure measured by said cylinder pressuredetector.

The present invention is directed also to an improved liquid deliverydevice having a first cylinder with a first reciprocating plunger and asecond cylinder with a second reciprocating plunger, a motor to drivesaid first and second plungers, a control unit to control operation ofsaid motor, a supply channel to feed an eluent from a supply source tothe inlet of said first cylinder, an inlet check valve fitted to saidsupply channel, an intermediate flow channel to introduce said eluentdischarged from the outlet of said first cylinder to the inlet of saidsecond cylinder, an outlet check valve fitted to said intermediate flowchannel, a discharge pressure detector to measure the discharge pressureof said eluent being discharged from said second cylinder, and acylinder pressure detector to measure the pressure of said eluentflowing in said first cylinder, wherein said improvement ischaracterized in that said control unit establishes the judgment pointbefore the pressure measured by said cylinder pressure detector agreeswith the pressure measured by said discharge pressure detector andcontrols the speed of rotation of said motor on the basis of thedischarge pressure measured by said discharge pressure detector and thepressure measured by said cylinder pressure detector.

The present invention is directed also to an improved method foroperating a liquid delivery device having a first cylinder with a firstreciprocating plunger and a second cylinder with a second reciprocatingplunger, a motor to drive said first and second plungers, a control unitto control operation of said motor, a supply channel to feed an eluentfrom a supply source to the inlet of said first cylinder, an inlet checkvalve fitted to said supply channel, an intermediate flow channel tointroduce said eluent discharged from the outlet of said first cylinderto the inlet of said second cylinder, an outlet check valve fitted tosaid intermediate flow channel, a discharge pressure detector to measurethe discharge pressure of said eluent being discharged from said secondcylinder, and a cylinder pressure detector to measure the pressure ofsaid eluent flowing in said first cylinder, with the liquid deliveryachieved by one reciprocating cycle of said first and second plungersbeing divided into three phases, wherein said improvement ischaracterized in that, in phase 1, said inlet check valve is opened andsaid outlet check valve is closed so that said eluent is sucked up bysaid first plunger and said eluent is discharged by said second plunger,phase 2 has the first half section for compression and the second halfsection for liquid delivery, in said compression section, said inletcheck valve and said outlet check valve are closed and said eluent whichhas been sucked up into said first cylinder is compressed, during whichsaid eluent is discharged by said second plunger, said eluent in saidfirst cylinder is compressed by said first plunger 1, as soon as thepressure (the pressure measured by said cylinder pressure detector) dueto this compression reaches the discharge pressure (the pressuremeasured by said discharge pressure detector) of said second cylinder,said outlet check valve 10 is opened and said compression section shiftsto said liquid delivery section, in said liquid delivery section, saidfirst plunger and said second plunger together force out said eluent, inphase 3, said inlet check valve is closed and said outlet check valve isopened, said second plunger sucks up said eluent, said first plunger 1discharges said eluent, this discharge is combined with the amount whichis sucked up by said second plunger, and said motor is controlled insuch a way that it runs fast in the compression section of phase 2 andit runs slow in the liquid delivery section of phase 2.

The present invention covers a liquid delivery device capable ofdelivering an eluent with a minimum fluctuation of pressure, a liquidchromatograph equipped with said liquid delivery device, and a methodfor operation of said liquid delivery device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram showing a liquid chromatograph with theliquid delivery device according to Example 1 of the present invention.

FIG. 2 is a diagram showing how the check valves move and the flow rateschange in response to the angle of cam rotation in Example 1 of thepresent invention.

FIG. 3 is a diagram showing the pressure change in the first cylinderthat occurs in the compression section in Example 1 of the presentinvention.

FIG. 4 a schematic diagram showing the liquid delivery device accordingto Example 2 of the present invention.

FIG. 5 is a diagram demonstrating the effect produced by Example 1 ofthe present invention.

FIG. 6 is a flow sheet showing the steps from the start of operation incompression section R (with the motor running at twice the normal speed)to the end of operation.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The examples of the present invention will be described below withreference to the accompanying drawings.

Example 1

The liquid chromatograph equipped with the liquid delivery device willbe outlined below with reference to FIG. 1.

The liquid chromatograph shown in FIG. 1 consists of a liquid deliverydevice 300, a sample injector 400, a column 500, a detector 600, and awaste storage 700.

The liquid delivery device 300 has a first cylinder 2 holding therein afirst plunger 1 and a second cylinder 4 holding therein a second plunger3. The plungers are made to reciprocate respectively by a first cam 5and a second cam 6.

These cams are driven by a motor 7, which is under control by a controlunit 8. The first cylinder 2 has an inlet and an outlet which areprovided respectively with an inlet check valve 9 and an outlet checkvalve 10. Thus, it sucks up an eluent 11 through the sucking side of theinlet check valve.

The first cylinder 2 has a cylinder pressure detector 12 to measure thepressure therein, and the second cylinder 4 has a discharge pressuredetector 13 to measure the pressure of liquid being discharged. Therotational shaft has a disk 14 attached thereto, which has slits tofacilitate detection of cam position by the cam position detectingsensor 15.

A term “supply channel” is used herein to denote the channel throughwhich the eluent 11 is supplied from the eluent reservoir to the inletof the first cylinder 2. The supply channel is provided with the inletcheck valve 9. A term “intermediate channel” is used herein to denotethe channel through which the eluent discharged from the outlet of thefirst cylinder 2 is introduced to the inlet of the second cylinder 4.The intermediate channel is provided with the outlet check valve 10.

FIG. 2 shows the movement of each part which corresponds to the rotatingangle of the cam.

That is, FIG. 2 shows timing at which the inlet check valve 9 and theoutlet check valve 10 open and close within one cycle (or onereciprocating motion of the plunger). It also shows the amount of eluentto be sucked up and discharged by the first plunger 1 and the secondplunger 3 and the total amount of liquid delivered by the liquiddelivery device in one cycle. It also shows the speed of motor rotationin terms of the angle of cam rotation.

The delivery of the eluent in one cycle is divided into three phases. Inphase 1, the first plunger 1 sucks up the eluent 11, with the checkvalve 9 remaining open and the check valve 10 remaining closed. Also, inphase 1, the second plunger 3 only works to deliver the eluent at aconstant flow rate Q.

Phase 2 is further divided into two sections—the first one forcompression and the second one for liquid delivery. In the first sectionof phase 2, the inlet check valve 9 and the outlet check valve 10 areclosed, so that the eluent 11 sucked up into the first cylinder 3 iscompressed. In this period, only the second plunger 3 discharges theeluent at a prescribed flow rate.

The eluent in the first cylinder is compressed by the first plunger 1until the pressure in the cylinder reaches the discharge pressure. At adesired pressure, the outlet check valve 10 opens and the second sectionof phase 2 starts for liquid delivery. In the section for liquiddelivery, the eluent is forced out by the first plunger 1 and the secondplunger 2.

In phase 3, the inlet check valve 9 remains closed and the outlet checkvalve 10 remains open. The second plunger 3 moves in such a direction asto suck up the eluent. The first plunger 1 discharges the eluent suchthat the amount of discharge is the sum of the prescribed amount of pumpdelivery Q and the amount sucked up by the second plunger.

The compression section R in phase 2 is varied in length according tothe discharging pressure of the liquid delivery device. Thus, the liquiddelivery device discharges the compressible eluent at a constant flowrate. The compression section R is extended or shortened in proportionto the pressure of the liquid being delivered.

There is a relation as explained below between the compression section Rand the flow rate Q (which is the amount of the eluent that is deliveredin a unit time). In the compression section R, the outlet check valve 10is closed, only the second plunger 3 delivers the eluent at a flow rateQ, and the first plunger 1 compresses the eluent which has been suckedup. In this way it is possible to deliver the compressible liquid at aconstant flow rate regardless of its degree of compression. Thistechnique is disclosed in Japanese Patent No. 3709409.

According to the disclosed technique, each cam is so curved as todeliver the eluent at Q/2 (or half the prescribed flow rate Q) and themotor 10 is run at twice the normal speed N in the compression section.In this process, the second plunger 3 delivers the eluent at a flow rateQ and the first plunger 1 compresses the eluent. As soon as thecompression section R is completed, the rotational speed of the motor 7returns from 2N to N (normal speed).

In the liquid delivery section of phase 2 and also in phase 3, theoutlet check valve 10 remains open. Therefore, in these periods, thefirst cylinder 2 and the second cylinder 4 have the same pressure. Whilethis state exists, the first pressure detector 12 and the secondpressure detector 13 are checked for their calibration.

Problems with this liquid delivery device are errors produced by the twopressure detectors.

Errors are unavoidable in any pressure detectors. They arise from noisein signals, fluctuation due to change in environment (such as ambienttemperature), and change with time. They also vary depending on the typeof eluent.

For example, if the value indicated by the cylinder pressure detector islower than the actual one (in which case the pressure in the firstcylinder 2 has reached the discharge pressure of the second cylinder 4),the system judges that further compression is necessary and causes themotor to run at twice the normal speed.

In this state, the outlet check valve remains open and both the pressuredetectors receive the same pressure. However, the cylinder pressuredetector 12 always reads a smaller value than the outlet pressuredetector 13, which results in the motor continuing to run at twice thenormal speed.

One way of avoiding this trouble in the conventional system was byreturning the rotational speed of the motor 7 to normal speed N assumingthat the two pressures have reached the same value before the differencebetween the reading of the outlet pressure detector and the reading ofthe cylinder pressure detector 12 actually becomes zero. Changing themotor speed in this manner decreases pressure and causes pulsation.

According to the present invention, the foregoing problem is addressedby establishing a point of judgment before the reading of the cylinderpressure detector agrees with the reading of the discharge pressuredetector (which is lower than the reading of the discharge pressuredetector), thereby calculating the point at which compression iscompleted. Controlling in this way prevents pressure fluctuation. Thehistory of compression helps calculate the point of completion ofcompression which permits adequate control.

FIG. 3 is a graph showing the change in pressure that occurs in thefirst cylinder during compression.

In this graph, the abscissa represents the angle of rotation of the camand the ordinate represents the change of pressure in the firstcylinder. As soon as the sucking of the eluent is complete, thecompression cycle starts. The starting point of the compression cycle isdetermined as the cam position detector 15 senses the cam angle. Asmentioned above, the motor 12 runs twice the normal speed in thecompression cycle.

First, the rate of change in pressure (denoted by K) is obtained after acertain length of period required for the system to stabilize, which ismeasured from the point at which the motor starts to run at twice thenormal speed in the compression cycle. The value of K, which representsthe slope of pressure increase in the first cylinder 2, is calculatedfrom the pressure increase (Pd) corresponding to the predetermined stepvalue (Ss) which is measured by the cylinder pressure detector 12.Incidentally, the motor 7 is a step motor whose angle of rotationdepends on the number of pulses.

Next, the extended period (or step value), denoted by Sa, is obtainedfrom Sa=Ss/Pd·Pa. Then, compression is continued, with the motor runningat twice the normal speed, until the judgment pressure (Pe=Pout−Pa)holds. Additional compression in this manner is carried out for a periodcorresponding to Sa. After that, the delivery of eluent is continued,with the motor running at the predetermined normal speed.

The number of steps (Sa), which corresponds to the extended period,equals that for Pa (the width of values established for pressure).

As soon as the judgment pressure (Pe) is reached, the motor is run forthe number of steps (Sa), which corresponds to Pa (the width of valuesestablished for pressure) previously obtained from K (the rate of changein pressure), and the compression section R in phase 2 (with the motorrunning twice the normal speed) terminates. Operation in this mannereliminates pulsation which results from the motor running at twice thenormal speed and the pressure decreasing in the conventional technology.

FIG. 3 shows the behavior of water, alcohol, and acetonitrile as theeluent. They vary in K (the rate of change in pressure) according asthey vary in compressibility. This problem is addressed by operation inthe foregoing manner which terminates the compression section R (withthe motor running twice the normal speed) which is calculated from K(the rate of change in pressure) for individual species of eluent. Inthis way it is possible to eliminate pulsation which results from themotor running at twice the normal speed and the pressure decreasing.

Incidentally, the motor 7 is a step motor as mentioned above. The highspeed rotation (at twice the normal speed) and the low speed rotationare controlled by the cam position detecting sensor 15. Control in thismanner is accomplished accurately because the step motor turns throughany angle in response to the number of pulses. Therefore, the step motorpermits accurately controlled rotation.

The motor 7 is controlled by the program stored in the control unit 8.

FIG. 6 is a flow chart showing steps from the start of the compressionsection R (with the motor running at twice the normal speed) to the endof operation.

In Step S101, the discharge pressure detector reads the dischargepressure (Pout) of the second cylinder. In Step S102, the judgmentpressure (Pe) is calculated from Pe=Pout−Pa (where Pa is the width ofpressure values which may be established arbitrarily).

The judgment pressure (Pe) is lower than the discharge pressure (Pout),and it occurs before compression is completed in the compression section(R) of phase 2.

In Step S103, the rate of change in pressure (K) in the first cylinderis measured and calculated from the initial part of phase 2 (K=Ss/Pd). Kvaries depending of the species, temperature, and aging of the eluent.The pressure of the first cylinder should be measured after it hasbecome stable, so that the rate of change in pressure (K) can bemeasured more adequately.

In Step S104, the point of completion of compression is calculated(Sa=K·Pa). In Step S105, the system confirms that the pressure of thefirst cylinder has reached the judgment pressure. In Step S106, themotor continues to rotate for a period equivalent to the extendedsection (Sa minutes) from the judgment point, and the compressionsection R (for the motor running twice the normal speed) terminates. Theforegoing steps are repeated.

The steps starting from the compression section R to the termination ofoperation are implemented according to programs stored in memory in thecontrol unit 8.

Example 2

FIG. 4 shows another example of the present invention.

This example demonstrates the so-called “high-pressure gradient” system,which is so designed as to deliver a mixture of solvents whose mixingratio varies gradually. The gradient system according to this example iscomprised of two units of the liquid delivery device described inExample 1. It has one pressure detector to measure the dischargepressure and control two pumps.

An ordinary high-pressure gradient system hardly produces a stable flowrate on account of two pumps interfering with each other. Thisinterference occurs when the pressure detector to control the flow rateof one pump is affected by pressure fluctuation arising from the actionof the other pump, and it disturbs control. This is not the case withthe present invention in which the read value of discharge pressure isnot used for control and hence no interference occurs. Thus thehigh-pressure gradient system according to the present invention is ableto deliver a mixture of solvents in a stable mixing ratio at a stableflow rate.

FIGS. 5( a) and 5(b) show respectively the effect produced without orwith control according to the present invention. The former suffersperiodic pressure decrease, whereas the latter is free of periodicdisturbance.

1. An improved liquid delivery device having cylinders arranged inseries in more than one stage, plungers reciprocating in said cylindersarranged in more than one stage, a motor to drive said plungers, acontrol unit to control operation of said motor, a discharge pressuredetector to control the discharge pressure of the liquid discharged fromthe cylinder in the last stage, and a cylinder pressure detector tomeasure the pressure of said liquid flowing in the cylinder in theinitial or middle stage, wherein said improvement is characterized inthat said control unit establishes the judgment point before thepressure measured by said cylinder pressure detector agrees with thepressure measured by said discharge pressure detector and controls thespeed of rotation of said motor on the basis of the discharge pressuremeasured by said discharge pressure detector and the pressure measuredby said cylinder pressure detector.
 2. An improved liquid deliverydevice having a first cylinder with a first reciprocating plunger and asecond cylinder with a second reciprocating plunger, a motor to drivesaid first and second plungers, a control unit to control operation ofsaid motor, a supply channel to feed an eluent from a supply source tothe inlet of said first cylinder, an inlet valve means fitted to saidsupply channel, an intermediate flow channel to introduce said eluentdischarged from the outlet of said first cylinder to the inlet of saidsecond cylinder, an outlet valve means fitted to said intermediate flowchannel, a discharge pressure detector to measure the discharge pressureof said eluent being discharged from said second cylinder, and acylinder pressure detector to measure the pressure of said eluentflowing in said first cylinder, wherein said improvement ischaracterized in that said control unit establishes the judgment pointbefore the pressure measured by said cylinder pressure detector agreeswith the pressure measured by said discharge pressure detector andcontrols the speed of rotation of said motor on the basis of thedischarge pressure measured by said discharge pressure detector and thepressure measured by said cylinder pressure detector.
 3. An improvedliquid delivery device having a first cylinder with a firstreciprocating plunger and a second cylinder with a second reciprocatingplunger, a motor to drive said first and second plungers, a control unitto control operation of said motor, a supply channel to feed a liquidfrom a supply source to the inlet of said first cylinder, an inlet checkvalve fitted to said supply channel, an intermediate flow channel tointroduce said liquid discharged from the outlet of said first cylinderto the inlet of said second cylinder, an outlet check valve fitted tosaid intermediate flow channel, a discharge pressure detector to measurethe discharge pressure of said liquid being discharged from said secondcylinder, and a cylinder pressure detector to measure the pressure ofsaid liquid flowing in said first cylinder, wherein said improvement ischaracterized in that said control unit establishes the judgment pointbefore the pressure measured by said cylinder pressure detector agreeswith the pressure measured by said discharge pressure detector andcontrols the speed of rotation of said motor on the basis of thedischarge pressure measured by said discharge pressure detector and thepressure measured by said cylinder pressure detector.
 4. The liquiddelivery device as defined in claim 3, wherein said control unit has acontrol function to change the speed of rotation of said motor when thepressure measured by said cylinder pressure detector reaches thedischarge pressure measured by said discharge pressure detector duringthe pressuring motion in which said first cylinder pressurizes saidliquid.
 5. The liquid delivery device as defined in claim 3, whereinsaid control unit has a control function to lower the speed of rotationof said motor when the pressure measured by said cylinder pressuredetector reaches the discharge pressure measured by said dischargepressure detector during the pressuring motion in which said firstcylinder pressurizes said liquid.
 6. The liquid delivery device asdefined in claim 3, wherein the values measured by said dischargepressure detector and said cylinder pressure detector are calibrated onthe basis of the values which are measured by said discharge pressuredetector and said cylinder pressure detector while said outlet checkvalue is open.